The object of this study is to determine the biochemical mechanisms that enable rare cells to grow in the presence of a metabolic analogue which is lethal for the great majority of cells in the population. Lines of Friend erythroleukemic cells, and other cancer cells, are grown in the presence of metabolic analogues. Surviving colonies are isolated, re-cloned, and then characterized biochemically. In some experiments, the cells are treated with a chemical mutagen prior to selection with the analogue. The analogues presently under study in this way are 6-azauridine and 5-fluoroorotic acid. Surviving clones are assayed for enzymes involved in pyrimidine synthesis and catabolism, as well as for certain related enzymes.